Variant 9-135663358-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000619315.2(LCN9):c.37A>G(p.Ile13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

LCN9
ENST00000619315.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.266

Variant links:

Genes affected

LCN9 (HGNC:17442): (lipocalin 9) Members of the lipocalin family, such as LCN9, have a common structure consisting of an 8-stranded antiparallel beta-barrel that forms a cup-shaped ligand-binding pocket or calyx. Lipocalins generally bind small hydrophobic ligands and transport them to specific cells (Suzuki et al., 2004 [PubMed 15363845]).[supplied by OMIM, Aug 2009]

LCN9 links:

LCN9 (HGNC:):

LCN9 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037367284).

BP6

Variant 9-135663358-A-G is Benign according to our data. Variant chr9-135663358-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3290305.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCN9	NM_001393661.1 linkuse as main transcript	c.37A>G	p.Ile13Val	missense_variant	1/6	ENST00000619315.2	NP_001380590.1
LCN9	NR_171893.1 linkuse as main transcript	n.50A>G		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LCN9	ENST00000619315.2 linkuse as main transcript	c.37A>G	p.Ile13Val	missense_variant	1/6	1	NM_001393661.1	ENSP00000482296.2	A0A087WZ21
LCN9	ENST00000277526.8 linkuse as main transcript	n.37A>G		non_coding_transcript_exon_variant	1/6	5		ENSP00000277526.4	Q8WX39
LCN9	ENST00000430290.6 linkuse as main transcript	n.23A>G		non_coding_transcript_exon_variant	1/6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461624

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 27, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.0050

DANN

Benign

0.17

DEOGEN2

Benign

0.0062

.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00033

LIST_S2

Benign

0.25

T;T

M_CAP

Benign

0.00060

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.35

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Benign

0.53

.;N

REVEL

Benign

0.025

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0020

.;B

Vest4

0.034

MutPred

0.39

Gain of catalytic residue at I13 (P = 0.1285);Gain of catalytic residue at I13 (P = 0.1285);

MVP

0.014

MPC

0.046

ClinPred

0.052

GERP RS

-0.53

Varity_R

0.015

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over